Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli.
A majority of E. coli proteins when overexpressed inhibit its growth, but the reasons behind overexpression toxicity of proteins remain unknown. Understanding the mechanism of overexpression toxicity is important from evolutionary, biotechnological and possibly clinical perspectives. Here we study s...
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| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064893&type=printable |
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| _version_ | 1850224810945150976 |
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| author | Gajinder Pal Singh Debasis Dash |
| author_facet | Gajinder Pal Singh Debasis Dash |
| author_sort | Gajinder Pal Singh |
| collection | DOAJ |
| description | A majority of E. coli proteins when overexpressed inhibit its growth, but the reasons behind overexpression toxicity of proteins remain unknown. Understanding the mechanism of overexpression toxicity is important from evolutionary, biotechnological and possibly clinical perspectives. Here we study sequence and functional features of cytosolic proteins of E. coli associated with overexpression toxicity to understand its mechanism. We find that number of positively charged residues is significantly higher in proteins showing overexpression toxicity. Very long proteins also show high overexpression toxicity. Among the functional classes, transcription factors and regulatory proteins are enriched in toxic proteins, while catalytic proteins are depleted. Overexpression toxicity could be predicted with reasonable accuracy using these few properties. The importance of charged residues in overexpression toxicity indicates that nonspecific electrostatic interactions resulting from protein overexpression cause toxicity of these proteins and suggests ways to improve the expression level of native and foreign proteins in E. coli for basic research and biotechnology. These results might also be applicable to other bacterial species. |
| format | Article |
| id | doaj-art-80cd7f22747d4923ac801015d6b0e01e |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-80cd7f22747d4923ac801015d6b0e01e2025-08-20T02:05:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6489310.1371/journal.pone.0064893Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli.Gajinder Pal SinghDebasis DashA majority of E. coli proteins when overexpressed inhibit its growth, but the reasons behind overexpression toxicity of proteins remain unknown. Understanding the mechanism of overexpression toxicity is important from evolutionary, biotechnological and possibly clinical perspectives. Here we study sequence and functional features of cytosolic proteins of E. coli associated with overexpression toxicity to understand its mechanism. We find that number of positively charged residues is significantly higher in proteins showing overexpression toxicity. Very long proteins also show high overexpression toxicity. Among the functional classes, transcription factors and regulatory proteins are enriched in toxic proteins, while catalytic proteins are depleted. Overexpression toxicity could be predicted with reasonable accuracy using these few properties. The importance of charged residues in overexpression toxicity indicates that nonspecific electrostatic interactions resulting from protein overexpression cause toxicity of these proteins and suggests ways to improve the expression level of native and foreign proteins in E. coli for basic research and biotechnology. These results might also be applicable to other bacterial species.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064893&type=printable |
| spellingShingle | Gajinder Pal Singh Debasis Dash Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. PLoS ONE |
| title | Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. |
| title_full | Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. |
| title_fullStr | Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. |
| title_full_unstemmed | Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. |
| title_short | Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli. |
| title_sort | electrostatic mis interactions cause overexpression toxicity of proteins in e coli |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0064893&type=printable |
| work_keys_str_mv | AT gajinderpalsingh electrostaticmisinteractionscauseoverexpressiontoxicityofproteinsinecoli AT debasisdash electrostaticmisinteractionscauseoverexpressiontoxicityofproteinsinecoli |